DNA 甲基化调控的 YTHDF2 与胶质瘤中的细胞迁移和免疫细胞浸润相关。

DNA methylation-regulated YTHDF2 correlates with cell migration and immune cell infiltration in glioma.

机构信息

Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.

Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650223, China.

出版信息

Aging (Albany NY). 2022 Jun 2;14(19):7774-7793. doi: 10.18632/aging.204104.

DOI:10.18632/aging.204104

PMID:35661004

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9596213/

Abstract

BACKGROUND

Glioma is a lethal malignant brain tumor, it comprises about 80% of all malignant brain tumours. Mounting evidence has reported that YTHDF2 plays a significant role in the cancer progression. However, the effects of YTHDF2 on the prognosis of low-grade gliomas (LGGs) and its correlation with tumor immune infiltration are unclear. The present study was designed to determine the biological functions of YTHDF2 in glioma and to evaluate the association of YTHDF2 expression with glioma progression.

METHODS

Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), as well as the Rembrandt and Gravendeel databases. The correlations among YTHDF2 expression, pathological characteristics, glioma progression and clinical outcome were evaluated. In addition, the correlation of YTHDF2 expression with immune cell infiltration was analyzed too.

RESULTS

We found that YTHDF2 was significantly up-regulated in LGGs which correlated with tumor grade and poor prognosis. Interestingly, we showed that YTHDF2 expression in LGG was associated with copy number variation, DNA hypomethylation, and induced transcription factor YY1. Besides, KEGG pathway analysis shows that YTHDF2 mainly participates in the immune response and oncogenic signaling pathway. Additionally, YTHDF2 is positively associated with diverse immune cells infiltration, immune cells, and multiple immune checkpoint molecules. Finally, we confirmed that YTHDF2 was highly expressed in LGGs tissues and correlated with the tumor grade with immunohistochemistry assay. More importantly, our results demonstrated that YTHDF2 was elevated in GBM cells. Knockdown of YTHDF2 significantly inhibits the proliferation and migration of GBM cells.

CONCLUSION

YTHDF2 correlates with glioma progression and immune cell infiltration, suggesting that YTHDF2 may be a useful prognostic biomarker for glioma.

摘要

背景

神经胶质瘤是一种致命的恶性脑肿瘤，约占所有恶性脑肿瘤的 80%。越来越多的证据表明 YTHDF2 在癌症进展中发挥着重要作用。然而，YTHDF2 对低级别神经胶质瘤（LGG）的预后的影响及其与肿瘤免疫浸润的相关性尚不清楚。本研究旨在确定 YTHDF2 在神经胶质瘤中的生物学功能，并评估 YTHDF2 表达与神经胶质瘤进展的关系。

方法

从癌症基因组图谱（TCGA）、中国神经胶质瘤基因组图谱（CGGA）、基因表达综合数据库（GEO）以及 Rembrandt 和 Gravendeel 数据库中获取神经胶质瘤患者的临床数据。评估 YTHDF2 表达与病理特征、神经胶质瘤进展和临床结局的相关性。此外，还分析了 YTHDF2 表达与免疫细胞浸润的相关性。

结果

我们发现 YTHDF2 在 LGG 中显著上调，与肿瘤分级和预后不良相关。有趣的是，我们表明 LGG 中的 YTHDF2 表达与拷贝数变异、DNA 低甲基化和诱导转录因子 YY1 有关。此外，KEGG 通路分析表明 YTHDF2 主要参与免疫反应和致癌信号通路。此外，YTHDF2 与多种免疫细胞浸润、免疫细胞和多个免疫检查点分子呈正相关。最后，我们通过免疫组织化学检测证实 YTHDF2 在 LGG 组织中高表达，并与肿瘤分级相关。更重要的是，我们的结果表明 YTHDF2 在 GBM 细胞中表达上调。YTHDF2 的敲低显著抑制了 GBM 细胞的增殖和迁移。